Artemin, a Member of the Glial Cell Line-derived Neurotrophic Factor Family of Ligands, is HER2-regulated and Mediates Acquired Trastuzumab Resistance by Promoting Cancer Stem Cell-like Behavior in Mammary Carcinoma Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Apr 17

PMID 24737320

Citations 20

Authors

Keshuo Ding

Arindam Banerjee

Sheng Tan

Junsong Zhao

Qian Zhuang

Rui Li

Pengxu Qian

Suling Liu

Zheng-Sheng Wu

Peter E Lobie

Tao Zhu

Affiliations

Soon will be listed here.

Abstract

Previous studies have demonstrated that Artemin (ARTN) functions as a cancer stem cell (CSC) and metastatic factor in mammary carcinoma. Herein, we report that ARTN mediates acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells. Ligands that increase HER2 activity increased ARTN expression in HER2-positive mammary carcinoma cells, whereas trastuzumab inhibited ARTN expression. Forced expression of ARTN decreased the sensitivity of HER2-positive mammary carcinoma cells to trastuzumab both in vitro and in vivo. Conversely, siRNA-mediated depletion of ARTN enhanced trastuzumab efficacy. Cells with acquired resistance to trastuzumab exhibited increased ARTN expression, the depletion of which restored trastuzumab sensitivity. Trastuzumab resistance produced an increased CSC population concomitant with enhanced mammospheric growth. ARTN mediated the enhancement of the CSC population by increased BCL-2 expression, and the CSC population in trastuzumab-resistant cells was abrogated upon inhibition of BCL-2. Hence, we conclude that ARTN is one mediator of acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells.

Citing Articles

Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics.

Alnasser S Stem Cells Int. 2023; 2023:8722803.

PMID: 38094260 PMC: 10719005. DOI: 10.1155/2023/8722803.

JHDM1D-AS1-driven inhibition of miR-940 releases ARTN expression to induce breast carcinogenesis.

Zuo Y, Ma M, Wen Y, Chang L, Qu C Clin Transl Oncol. 2023; 25(7):2192-2203.

PMID: 36862282 DOI: 10.1007/s12094-023-03102-y.

Identification of immune-related signature for the prognosis and benefit of immunotherapy in triple-negative breast cancer.

Sun X, Zhang T Front Genet. 2022; 13:1067254.

PMID: 36452159 PMC: 9701826. DOI: 10.3389/fgene.2022.1067254.

The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers.

Li Q, Cao Z, Zhao S Int J Med Sci. 2022; 19(4):659-668.

PMID: 35582425 PMC: 9108399. DOI: 10.7150/ijms.64133.

Evolution of gene expression signature in mammary gland stem cells from neonatal to old mice.

Huang X, Xu Y, Qian L, Zhao Q, Liu P, Lu J Cell Death Dis. 2022; 13(4):335.

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